Home > A. Molecular pathology > EGFR

EGFR

HGNC:3236 MIM.131550 7p12.3-p12.1

Saturday 6 November 2004

Epithelial growth factor receptor (EGFR) appears as a key element in colorectal carcinogenesis. It displays high levels of expression.

EGFR activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed.

For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats.

Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux (cetuximab), and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system for immunohistochemistry.

No correlation has been found so far between EGFR level of expression and response to cetuximab. (#16387663#)

Pathology

- EGFR gene amplification by amp(7)(p12) and EGFR overexpression in various cancers

  • glioblastoma (34%)
  • anaplastic oligodendroglioma

- germline mutations

  • non-small cell lung cancer predisposition (#16258541#)

- somatic mutations

  • non-small cell lung cancers
    • Somatic activating mutations in EGFR identify a subset of non-small cell lung cancer that respond to tyrosine kinase inhibitors.
    • acquisition of drug resistance (somatic EGFR-T790M) (#16258541#)

A test for the EGFR mutation in cancer patients has been developed by Genzyme. EGFR mutations have been shown to correlate with clinical response to certain drugs, including Tarceva® (erlotinib) and IRESSA® (gefitinib), used in treating this deadly form of cancer.

Main mutants

- T790M-EGFR

EGFR-inhibitors

- gefitinib

  • gefitinib inhibits the tyrosine kinase activity of EGFR, the receptor for EGF (epidermal growth factor)

- cetuximab
- panitumumab
- erlotinib

Links

- Animation of the organisation and function of the Ras-Raf-MEK-ERK pathway at Expert Reviews in Molecular Medicine

Reviews

- Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007 Mar;7(3):169-81. PMID: #17318210#

- Nyati MK, Morgan MA, Feng FY, Lawrence TS. Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 2006 Nov;6(11):876-85. PMID: #17036041#

- Herbst RS, Fukuoka M, Baselga J. Gefitinib—a novel targeted approach to treating cancer. Nat Rev Cancer. 2004 Dec;4(12):956-65. PMID: #15573117#

- Carpenter G. The EGF receptor: a nexus for trafficking and signaling. Bioessays. 2000 Aug;22(8):697-707. PMID: #10918300#

References

- Mapping EGFR1 mutations in patients with lung adenocarcinoma. Vlastos F, Zinszner J, Hussenet T, du Manoir S, Vordonis L, Nikolakopoulou S, Hardavella G, Lacomme S, Vignaud JM, Martinet N. Diagn Mol Pathol. 2010 Dec;19(4):209-17. PMID: #21052000#

- Hijiya N, Miyawaki M, Kawahara K, Akamine S, Tsuji K, Kadota J, Akizuki S, Uchida T, Matsuura K, Tsukamoto Y, Moriyama M. Phosphorylation status of epidermal growth factor receptor is closely associated with responsiveness to gefitinib in pulmonary adenocarcinoma. Hum Pathol. 2008 Mar;39(3):316-23. PMID: #18261621#

- Ch’ng S, Low I, Ng D, Brasch H, Sullivan M, Davis P, Tan ST. Epidermal growth factor receptor: a novel biomarker for aggressive head and neck cutaneous squamous cell carcinoma. Hum Pathol. 2008 Mar;39(3):344-9. Epub 2007 Nov 28. PMID: #18045646#